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By 2017 estimates, diabetes mellitus affects 425 million people globally; approximately 90–95% of these have type 2 diabetes. This narrative review highlights two domains of sex differences related to the burden of type 2 diabetes across the life span: sex differences in the prevalence and incidence of type 2 diabetes, and sex differences in the cardiovascular burden conferred by type 2 diabetes. In the presence of type 2 diabetes, the difference in the absolute rates of cardiovascular disease (CVD) between men and women lessens, albeit remaining higher in men. Large-scale observational studies suggest that type 2 diabetes confers 25–50% greater excess risk of incident CVD in women compared with men. Physiological and behavioural mechanisms that may underpin both the observed sex differences in the prevalence of type 2 diabetes and the associated cardiovascular burden are discussed in this review. Gender differences in social behavioural norms and disparities in provider-level treatment patterns are also highlighted, but not described in detail. We conclude by discussing research gaps in this area that are worthy of further investigation.

There is evidence from human twin and family studies as well as mouse and rat selection experiments that there are considerable interindividual differences in the response of cardiorespiratory fitness (CRF) and other cardiometabolic traits to a given exercise programme dose. We developed this consensus statement on exercise response variability following a symposium dedicated to this topic. There is strong evidence from both animal and human studies that exercise training doses lead to variable responses. A genetic component contributes to exercise training response variability.In this consensus statement, we (1) briefly review the literature on exercise response variability and the various sources of variations in CRF response to an exercise programme, (2) introduce the key research designs and corresponding statistical models with an emphasis on randomised controlled designs with or without multiple pretests and post-tests, crossover designs and repeated measures designs, (3) discuss advantages and disadvantages of multiple methods of categorising exercise response levels—a topic that is of particular interest for personalised exercise medicine and (4) outline approaches that may identify determinants and modifiers of CRF exercise response. We also summarise gaps in knowledge and recommend future research to better understand exercise response variability.

Background Low bone mineral density (BMD) and subsequent fractures are a major public health problem in postmenopausal women. The purpose of this study was to use the aggregate data meta-analytic approach to examine the effects of ground (for example, walking) and/or joint reaction (for example, strength training) exercise on femoral neck (FN) and lumbar spine (LS) BMD in postmenopausal women. Methods The a priori inclusion criteria were: (1) randomized controlled trials, (2) exercise intervention ≥ 24 weeks, (3) comparative control group, (4) postmenopausal women, (5) participants not regularly active, i.e., less than 150 minutes of moderate intensity (3.0 to 5.9 metabolic equivalents) weight bearing endurance activity per week, less than 75 minutes of vigorous intensity (> 6.0 metabolic equivalents) weight bearing endurance activity per week, resistance training < 2 times per week, (6) published and unpublished studies in any language since January 1, 1989, (7) BMD data available at the FN and/or LS. Studies were located by searching six electronic databases, cross-referencing, hand searching and expert review. Dual selection of studies and data abstraction were performed. Hedge’s standardized effect size ( g ) was calculated for each FN and LS BMD result and pooled using random-effects models. Z -score alpha values, 95%confidence intervals (CI) and number-needed-to-treat (NNT) were calculated for pooled results. Heterogeneity was examined using Q and I 2 . Mixed-effects ANOVA and simple meta-regression were used to examine changes in FN and LS BMD according to selected categorical and continuous variables. Statistical significance was set at an alpha value ≤0.05 and a trend at >0.05 to ≤ 0.10. Results Small, statistically significant exercise minus control group improvements were found for both FN (28  g’s , 1632 participants, g  = 0.288, 95% CI = 0.102, 0.474, p  = 0.002, Q = 90.5, p  < 0.0001, I 2  = 70.1%, NNT = 6) and LS (28  g’s , 1504 participants, g  = 0.179, 95% CI = −0.003, 0.361, p  = 0.05, Q = 77.7, p  < 0.0001, I 2  = 65.3%, NNT = 6) BMD. Clinically, it was estimated that the overall changes in FN and LS would reduce the 20-year relative risk of osteoporotic fracture at any site by approximately 11% and 10%, respectively. None of the mixed-effects ANOVA analyses were statistically significant. Statistically significant, or a trend for statistically significant, associations were observed for changes in FN and LS BMD and 20 different predictors. Conclusions The overall findings suggest that exercise may result in clinically relevant benefits to FN and LS BMD in postmenopausal women. Several of the observed associations appear worthy of further investigation in well-designed randomized controlled trials.

Exercise confers short-term benefits for individuals with Parkinson disease (PD). The purpose of the study was to compare short- and long-term responses among 2 supervised exercise programs and a home-based control exercise program. The 16-month randomized controlled exercise intervention investigated 3 exercise approaches: flexibility/balance/function exercise (FBF), supervised aerobic exercise (AE), and home-based exercise (control). This study was conducted in outpatient clinics. The participants were 121 individuals with PD (Hoehn & Yahr stages 1-3). The FBF program (individualized spinal and extremity flexibility exercises followed by group balance/functional training) was supervised by a physical therapist. The AE program (using a treadmill, bike, or elliptical trainer) was supervised by an exercise trainer. Supervision was provided 3 days per week for 4 months, and then monthly (16 months total). The control group participants exercised at home using the National Parkinson Foundation Fitness Counts program, with 1 supervised, clinic-based group session per month. Outcomes, obtained by blinded assessors, were determined at 4, 10, and 16 months. The primary outcome measures were overall physical function (Continuous Scale-Physical Functional Performance [CS-PFP]), balance (Functional Reach Test [FRT]), and walking economy (oxygen uptake [mL/kg/min]). Secondary outcome measures were symptom severity (Unified Parkinson's Disease Rating Scale [UPDRS] activities of daily living [ADL] and motor subscales) and quality of life (39-item Parkinson's Disease Quality of Life Scale [PDQ-39]). Of the 121 participants, 86.8%, 82.6%, and 79.3% completed 4, 10, and 16 months, respectively, of the intervention. At 4 months, improvement in CS-PFP scores was greater in the FBF group than in the control group (mean difference=4.3, 95% confidence interval [CI]=1.2 to 7.3) and the AE group (mean difference=3.1, 95% CI=0.0 to 6.2). Balance was not different among groups at any time point. Walking economy improved in the AE group compared with the FBF group at 4 months (mean difference=-1.2, 95% CI=-1.9 to -0.5), 10 months (mean difference=-1.2, 95% CI=-1.9 to -0.5), and 16 months (mean difference=-1.7, 95% CI=-2.5 to -1.0). The only secondary outcome that showed significant differences was UPDRS ADL subscale scores: the FBF group performed better than the control group at 4 months (mean difference=-1.47, 95% CI=-2.79 to -0.15) and 16 months (mean difference=-1.95, 95% CI=-3.84 to -0.08). Absence of a non-exercise control group was a limitation of the study. Findings demonstrated overall functional benefits at 4 months in the FBF group and improved walking economy (up to 16 months) in the AE group.

The recovery of quadriceps muscle force and function after total knee arthroplasty (TKA) is suboptimal, which predisposes patients to disability with increasing age. The purpose of this investigation was to evaluate the efficacy of quadriceps muscle neuromuscular electrical stimulation (NMES), initiated 48 hours after TKA, as an adjunct to standard rehabilitation. This was a prospective, longitudinal randomized controlled trial. Sixty-six patients, aged 50 to 85 years and planning a primary unilateral TKA, were randomly assigned to receive either standard rehabilitation (control) or standard rehabilitation plus NMES applied to the quadriceps muscle (initiated 48 hours after surgery). The NMES was applied twice per day at the maximum tolerable intensity for 15 contractions. Data for muscle strength, functional performance, and self-report measures were obtained before surgery and 3.5, 6.5, 13, 26, and 52 weeks after TKA. At 3.5 weeks after TKA, significant improvements with NMES were found for quadriceps and hamstring muscle strength, functional performance, and knee extension active range of motion. At 52 weeks, the differences between groups were attenuated, but improvements with NMES were still significant for quadriceps and hamstring muscle strength, functional performance, and some self-report measures. Treatment volume was not matched for both study arms; NMES was added to the standard of care treatment. Furthermore, testers were not blinded during testing, but used standardized scripts to avoid bias. Finally, some patients reached the maximum stimulator output during at least one treatment session and may have tolerated more stimulation. The early addition of NMES effectively attenuated loss of quadriceps muscle strength and improved functional performance following TKA. The effects were most pronounced and clinically meaningful within the first month after surgery, but persisted through 1 year after surgery.

Background/rationale Although TKA reliably reduces pain from knee osteoarthritis, full recovery of muscle strength and physical function to normal levels is rare. We presumed that a better understanding of acute changes in hamstrings and quadriceps muscle performance would allow us to enhance early rehabilitation after TKA and improve long-term function. Questions/purposes The purposes of this study were to (1) evaluate postoperative quadriceps and hamstrings muscle strength loss after TKA and subsequent recovery using the nonoperative legs and healthy control legs for comparison, and (2) measure hamstrings coactivation before and after TKA during a maximal isometric quadriceps muscle contraction and compare with nonoperative and healthy control legs. Methods We prospectively followed 30 patients undergoing TKA at 2 weeks preoperatively and 1, 3, and 6 months postoperatively and compared patient outcomes with a cross-sectional cohort of 15 healthy older adults. Bilateral, isometric strength of the quadriceps and hamstrings was assessed along with EMG measures of hamstrings coactivation during a maximal isometric quadriceps contraction. Results There were no differences in strength loss or recovery between the quadriceps and hamstrings muscles of the operative leg throughout the followup, although differences existed when compared with nonoperative and healthy control legs. Hamstrings muscle coactivation in the operative leg during a maximal quadriceps effort was elevated at 1 month (144.5%) compared to the nonoperative leg. Conclusions Although quadriceps dysfunction after TKA typically is recognized and addressed in postoperative therapy protocols, hamstrings dysfunction also is present and should be addressed. Clinical Relevance Quadriceps and hamstrings muscle strengthening should be the focus of future rehabilitation programs to optimize muscle function and long-term outcomes.

Neuromuscular electrical stimulation (NMES) can facilitate the recovery of quadriceps muscle strength after total knee arthroplasty (TKA), yet the optimal intensity (dosage) of NMES and its effect on strength after TKA have yet to be determined. The primary objective of this study was to determine whether the intensity of NMES application was related to the recovery of quadriceps muscle strength early after TKA. A secondary objective was to quantify quadriceps muscle fatigue and activation immediately after NMES to guide decisions about the timing of NMES during rehabilitation sessions. This study was an observational experimental investigation. Data were collected from 30 people who were 50 to 85 years of age and who received NMES after TKA. These people participated in a randomized controlled trial in which they received either standard rehabilitation or standard rehabilitation plus NMES to the quadriceps muscle to mitigate strength loss. For the NMES intervention group, NMES was applied 2 times per day at the maximal tolerable intensity for 15 contractions beginning 48 hours after surgery over the first 6 weeks after TKA. Neuromuscular electrical stimulation training intensity and quadriceps muscle strength and activation were assessed before surgery and 3.5 and 6.5 weeks after TKA. At 3.5 weeks, there was a significant association between NMES training intensity and a change in quadriceps muscle strength (R(2)=.68) and activation (R(2)=.22). At 6.5 weeks, NMES training intensity was related to a change in strength (R(2)=.25) but not to a change in activation (R(2)=.00). Furthermore, quadriceps muscle fatigue occurred during NMES sessions at 3.5 and 6.5 weeks, whereas quadriceps muscle activation did not change. Some participants reached the maximal stimulator output during at least 1 treatment session and might have tolerated more stimulation. Higher NMES training intensities were associated with greater quadriceps muscle strength and activation after TKA.

ABSTRACT Compromised bone structural and mechanical properties are implicated in the increased fracture risk in type 1 diabetes (T1D). We investigated bone structure and turnover by histomorphometry in postmenopausal women with T1D and controls without diabetes using tetracycline double‐labeled transiliac bone biopsy. After in vivo tetracycline double labeling, postmenopausal women with T1D of at least 10 years and without diabetes underwent transiliac bone biopsy. An expert blinded to the study group performed histomorphometry. Static and dynamic histomorphometry measurements were performed and compared between the two groups. The analysis included 9 postmenopausal women with T1D (mean age 58.4 ± 7.1 years with 37.9 ± 10.9 years of diabetes and HbA1c 7.1% ± 0.4%) and 7 postmenopausal women without diabetes (mean age 60.9 ± 3.3 years and HbA1c 5.4% ± 0.2%). There were no significant differences in serum PTH (38.6 ± 8.1 versus 51.9 ± 23.9 pg/mL), CTX (0.4 ± 0.2 versus 0.51 ± 0.34 ng/mL), or P1NP (64.5 ± 26.2 versus 87.3 ± 45.3 ng/mL). Serum 25‐hydroxyvitamin D levels were higher in T1D than in controls (53.1 ± 20.8 versus 30.9 ± 8.2 ng/mL, p < 0.05). Bone structure metrics (bone volume, trabecular thickness, trabecular number, and cortical thickness) were similar between the groups. Indices of bone formation (osteoid volume, osteoid surface, and bone formation rate) were 40% lower in T1D and associated with lower activation frequency. However, the differences in bone formation were not statistically significant. Long‐standing T1D may affect bone turnover, mainly bone formation, without significantly affecting bone structure. Further research is needed to understand bone turnover and factors affecting bone turnover in people with T1D. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research. Bone Turnover in Postmenopausal women with T1D.

Objective. Examine the effects of exercise on femoral neck (FN) and lumbar spine (LS) bone mineral density (BMD) in premenopausal women. Methods. Meta-analysis of randomized controlled exercise trials ≥24 weeks in premenopausal women. Standardized effect sizes (g) were calculated for each result and pooled using random-effects models, Z score alpha values, 95% confidence intervals (CIs), and number needed to treat (NNT). Heterogeneity was examined using Q and I2. Moderator and predictor analyses using mixed-effects ANOVA and simple metaregression were conducted. Statistical significance was set at P≤0.05. Results. Statistically significant improvements were found for both FN (7g's, 466 participants, g=0.342, 95%  CI=0.132, 0.553, P=0.001, Q=10.8, P=0.22, I2=25.7%, NNT=5) and LS (6g's, 402 participants, g=0.201, 95%  CI=0.009, 0.394, P=0.04, Q=3.3, P=0.65, I2=0%, NNT=9) BMD. A trend for greater benefits in FN BMD was observed for studies published in countries other than the United States and for those who participated in home versus facility-based exercise. Statistically significant, or a trend for statistically significant, associations were observed for 7 different moderators and predictors, 6 for FN BMD and 1 for LS BMD. Conclusions. Exercise benefits FN and LS BMD in premenopausal women. The observed moderators and predictors deserve further investigation in well-designed randomized controlled trials. Erratum to “Exercise and Bone Mineral Density in Premenopausal Women: A Meta-Analysis of Randomized Controlled Trials”dx.doi.org/10.1155/2013/583217

Background/ObjectivesThe doubly labeled water (DLW) method is the gold standard methodology for determination of free-living, total daily energy expenditure (TEE). However, there is no single accepted approach for either the sampling protocols (daily vs. two-point, in which samples are collected after dosing and at the end of the measurement period) or the calculations used in the determination of the rate of carbon dioxide production (rCO2) and TEE. Moreover, fluctuations in natural background abundances introduce error in the calculation of rCO2 and TEE. The advent of new technologies makes feasible the possibility of including additional isotope measures (17O) to account for background variation, which may improve accuracy.Subjects/MethodsSixteen subjects were studied for 7 consecutive days in a whole-room indirect calorimeter (IC) with concurrent measurement of TEE by DLW. Daily urine samples were obtained and isotope ratios were determined using off-axis integrated cavity output spectroscopy (OA-ICOS).ResultsWe determined the best combination of approaches for estimating dilution spaces and elimination rates and calculated average daily volume of carbon dioxide production (VCO2) using six different published equations. Using this best combination, multi-point fitting of isotope elimination rates using the daily urine samples substantially improved the average precision (4.5% vs. 6.0%) and accuracy (−0.5% vs. −3.0%) compared with the two-point method. This improvement may partly reflect the less variable day-to-day chamber measurements of energy expenditure. Utilizing 17O measurements to correct for errors due to background isotope fluctuations provided additional but minor improvements in precision (4.2% vs. 4.5%) and accuracy (0.2% vs. 0.5%).ConclusionsThis work shows that optimizing sampling and calculation protocols can improve the accuracy and precision of DLW measurements.